Aryl- and -heteroarylalkylcarbamate derivatives are known to be useful in the treatment of numerous metabolic diseases in varying degrees. Their preparation and their application in therapeutics is also well documented.
Phenylalkylcarbamate and (dioxan-2-yl)alkylcarbamate derivatives, disclosed respectively in the documents FR 2850377 A and WO 2004/020430 A2, which are inhibitors of the enzyme FAAH (Fatty Acid Amido Hydrolase) are already known and are incorporated herein by reference.
However, there still exists a need to find and develop products which are inhibitors of the enzyme FAAH. The compounds of the present invention can readly acheve this objective.
The compounds of the invention correspond to the general formula (I):

in which:
A is chosen from one or more groups X, Y and/or Z;
X represents a methylene group optionally substituted by one or two C1-6-alkyl, C3-7-cycloalkyl or C3-7-cycloalkyl-C1-3-alkylene groups;
Y represents either a C2-alkenylene group optionally substituted by one or two C1-6-alkyl, C3-7-cycloalkyl or C3-7-cycloalkyl-C1-3-alkylene groups; or a C2-alkynylene group;
Z represents a group of formula:

m represents an integer ranging from 1 to 5;
p and q represent integers and are defined such that p+q is a number ranging from 1 to 5;
n represents an integer ranging from 1 to 7;
R1 represents an R2 group optionally substituted by one or more R3 and/or R4 groups;
R2 represents a group chosen from a pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, naphthyl, quinolinyl, tetrahydroquinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, 2-oxo-3,4-dihydroquinolinyl, 1-oxo-3,4-dihydroisoquinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, naphthyridinyl, benzofuranyl, dihydrobenzofuranyl, benzothienyl, dihydrobenzothienyl, indolyl, indolinyl, indazolyl, isoindolyl, benzimidazolyl, benzoxazolyl benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzoxadiazolyl, benzothiadiazolyl, pyrrolopyridyl, furopyridyl, thienopyridyl, imidazopyridyl, oxazolopyridyl, thiazolopyridyl, pyrazolopyridyl, isoxazolopyridyl or isothiazolopyridyl;
R3 represents a group chosen from halogen atoms or cyano, nitro, C1-6-alkyl, C3-7-cycloalkyl, C1-6-alkoxy, hydroxyl, C1-6-thioalkyl, C1-6-fluoroalkyl, C1-6-fluoroalkoxy, C1-6-fluorothioalkyl, NR5R6, NR5COR6, NR5CO2R6, NR5SO2R6, COR5, CO2R5, CONR5R6, SO2R5, SO2NR5R6, —O—(C1-3-alkylene)-O— or phenyl groups, the phenyl group optionally being substituted by one or more halogen atoms;
R4 represents a group chosen from phenyl, phenyloxy, benzyloxy, naphthyl, pyridyl, pyrimidinyl, pyridazinyl or pyrazinyl groups; it being possible for the R4 group or groups to be substituted by one or more R3 groups which are identical to or different from one another;
R5 and R6 represent, independently of one another, a hydrogen atom or a C1-6-alkyl group or form, with the atom or atoms which carry them, a ring chosen from an azetidine, pyrrolidine, piperidine, morpholine, thiomorpholine, azepine or piperazine ring, this ring optionally being substituted by a C1-6-alkyl or benzyl group;
R7 represents a hydrogen atom or a C1-6-alkyl group;
R8 represents a hydrogen atom or a C1-6-alkyl, C3-7-cycloalkyl or C3-7-cycloalkyl-C1-3-alkylene group.
In the context of the invention, the compounds of general formula (I) can thus comprise several groups A which are identical to or different from one another.
Among the compounds of general formula (I), a first subgroup of compounds is comprised of compounds for which:
A is chosen from one or more groups X and/or Y;
X represents a methylene group;
Y represents a C2-alkynylene group;
n represents an integer ranging from 1 to 5;
R1 represents an R2 group optionally substituted by one or more R3 and/or R4 groups;
R2 represents a group chosen from a pyridyl, pyrimidinyl, pyridazinyl, imidazolyl, oxazolyl, pyrazolyl, isoxazolyl, oxadiazolyl, naphthyl, quinolinyl, isoquinolinyl, dihydroisoquinolinyl, 2-oxo-3,4-dihydroquinolinyl, indolyl, benzimidazolyl or pyrrolopyridyl;
R3 represents a group chosen from halogen atoms, more particularly chlorine and fluorine atoms, or C1-6-alkyl, more particularly methyl, C3-7-cycloalkyl, more particularly cyclopropyl, C1-6-alkoxy, more particularly methoxy, NR5R6 or phenyl groups;
R4 represents a group chosen from phenyl, naphthyl or pyridyl groups; it being possible for the R4 group or groups to be substituted by one or more R3 groups which are identical to or different from one another;
R5 and R6 represent, independently of one another, a C1-6-alkyl group, more particularly a methyl;
R7 represents a hydrogen atom or a C1-6-alkyl group;
R8 represents a hydrogen atom or a C1-6-alkyl, C3-7-cycloalkyl or C3-7-cycloalkyl-C1-3-alkylene group.
Among the compounds of general formula (I), a second subgroup of compounds is comprised of the compounds for which:
A, X, Y, Z, m, p, q, n, R1, R3, R4, R5, R6, R7 and R8 are as defined in the general formula (I) or in the first subgroup as defined above,
and R2 represents a group chosen from a pyridyl, pyrimidinyl, oxazolyl, isoxazolyl, naphthyl, quinolinyl or isoquinolinyl.
Among the compounds of general formula (I), a third subgroup of compounds is comprised of the compounds for which:
A, X, Y, Z, m, p, q, n, R1, R2, R3, R4, R5 and R6 are as defined in the general formula (I) or in the subgroups as defined above;
R7 represents a hydrogen atom;
R8 represents a hydrogen atom or a C1-6-alkyl group, more particularly a methyl.
The following compounds may be mentioned among the compounds of the subgroups defined above:    2-(methylamino)-2-oxoethyl (5-phenylpyrid-2-yl)methylcarbamate    2-(methylamino)-2-oxoethyl 2-(5-phenylpyrid-2-yl)ethylcarbamate    2-(methylamino)-2-oxoethyl 2-(6-phenylpyrid-3-yl)ethylcarbamate    2-(methylamino)-2-oxoethyl 2-(2-phenylpyrimidin-5-yl)ethylcarbamate    2-(methylamino)-2-oxoethyl 2-(5-phenylpyrimidin-2-yl)ethylcarbamate    2-(methylamino)-2-oxoethyl 2-[6-(4-chlorophenyl)pyrimidin-4-yl]ethylcarbamate    2-(methylamino)-2-oxoethyl 2-[6-(4-chlorophenyl)-2-methylpyrimidin-4-yl]ethylcarbamate    2-(methylamino)-2-oxoethyl 2-[6-(4-chlorophenyl)-2-(dimethylamino)pyrimidin-4-yl]ethylcarbamate    2-(methylamino)-2-oxoethyl 2-(isoquinolin-7-yl)ethylcarbamate    2-(methylamino)-2-oxoethyl 2-(2-phenyl-1,3-oxazol-4-yl)ethylcarbamate    2-(methylamino)-2-oxoethyl 2-[5-(4-chlorophenyl)isoxazol-3-yl]ethylcarbamate    2-amino-2-oxoethyl 3-(pyrid-2-yl)propylcarbamate    2-amino-2-oxoethyl 3-(pyrid-3-yl)propylcarbamate    2-amino-2-oxoethyl 3-(pyrid-4-yl)propylcarbamate    2-amino-2-oxoethyl 3-(pyrimidin-5-yl)propylcarbamate    2-(methylamino)-2-oxoethyl 3-[6-(4-chlorophenyl)pyrimidin-4-yl]propylcarbamate    2-(methylamino)-2-oxoethyl 3-[6-(4-chlorophenyl)-2-methylpyrimidin-4-yl]propylcarbamate    2-(methylamino)-2-oxoethyl 3-[6-(4-chlorophenyl)-2-(dimethylamino)pyrimidin-4-yl]propylcarbamate    2-amino-2-oxoethyl 3-(quinolin-2-yl)propylcarbamate    2-amino-2-oxoethyl 3-(quinolin-4-yl)propylcarbamate    2-amino-2-oxoethyl 3-(isoquinolin-1-yl)propylcarbamate    2-amino-2-oxoethyl 3-(isoquinolin-4-yl)propylcarbamate    2-(methylamino)-2-oxoethyl 3-[5-(4-chlorophenyl)isoxazol-3-yl]propylcarbamate    2-amino-2-oxoethyl 3-[3-(4-chlorophenyl)isoxazol-5-yl]propylcarbamate    2-(methylamino)-2-oxoethyl 3-[3-(4-chlorophenyl)isoxazol-5-yl]propylcarbamate    2-(methylamino)-2-oxoethyl 3-[3-(4-phenylphenyl)isoxazol-5-yl]propylcarbamate    2-(methylamino)-2-oxoethyl 3-[3-(naphth-2-yl)isoxazol-5-yl]propylcarbamate    2-amino-2-oxoethyl 4-(pyrid-2-yl)butylcarbamate    2-amino-2-oxoethyl 4-(pyrid-3-yl)butylcarbamate    2-amino-2-oxoethyl 4-(pyrid-4-yl)butylcarbamate    2-amino-2-oxoethyl 4-(pyrimidin-5-yl)butylcarbamate    2-(methylamino)-2-oxoethyl 4-[6-(4-chlorophenyl)pyrimidin-4-yl]butylcarbamate    2-(methylamino)-2-oxoethyl 4-[6-(4-chlorophenyl)-2-methylpyrimidin-4-yl]butylcarbamate    2-(methylamino)-2-oxoethyl 4-[6-(4-chlorophenyl)-2-cyclopropylpyrimidin-4-yl]butylcarbamate    2-(methylamino)-2-oxoethyl 4-[6-(4-chlorophenyl)-2-(dimethylamino)pyrimidin-4-yl]butylcarbamate    2-amino-2-oxoethyl 4-(quinolin-2-yl)butylcarbamate    2-amino-2-oxoethyl 4-(quinolin-4-yl)butylcarbamate    2-amino-2-oxoethyl 4-(isoquinolin-1-yl)butylcarbamate    2-amino-2-oxoethyl 4-(isoquinolin-4-yl)butylcarbamate    2-(methylamino)-2-oxoethyl 4-[5-(4-chlorophenyl)isoxazol-3-yl]butylcarbamate    2-(methylamino)-2-oxoethyl 4-[3-(4-chlorophenyl)isoxazol-5-yl]butylcarbamate    2-(methylamino)-2-oxoethyl 4-[3-(4-phenylphenyl)isoxazol-5-yl]butylcarbamate    2-(methylamino)-2-oxoethyl 4-[3-(naphth-2-yl)isoxazol-5-yl]butylcarbamate    2-amino-2-oxoethyl 5-(pyrid-2-yl)pentylcarbamate    2-amino-2-oxoethyl 5-(pyrid-4-yl)pentylcarbamate    2-amino-2-oxoethyl 5-(pyrimidin-5-yl)pentylcarbamate    2-amino-2-oxoethyl 5-(quinolin-2-yl)pentylcarbamate    2-amino-2-oxoethyl 5-(quinolin-4-yl)pentylcarbamate    2-amino-2-oxoethyl 5-(isoquinolin-1-yl)pentylcarbamate    2-amino-2-oxoethyl 5-(isoquinolin-4-yl)pentylcarbamate    2-amino-2-oxoethyl [3-(naphth-1-yl)prop-2-yn-1-yl]carbamate    2-(methylamino)-2-oxoethyl [3-(naphth-1-yl)prop-2-yn-1-yl]carbamate    2-amino-2-oxoethyl [5-(naphth-1-yl)pent-4-yn-1-yl]carbamate    2-(methylamino)-2-oxoethyl [5-(naphth-1-yl)pent-4-yn-1-yl]carbamate    2-(methylamino)-2-oxoethyl [5-(4-fluoronaphth-1-yl)pent-4-yn-1-yl]carbamate    2-(methylamino)-2-oxoethyl [3-(pyrid-3-yl)isoxazol-5-ylpropyl]carbamate    2-(methylamino)-2-oxoethyl [3-(4-methoxynaphth-1-yl)isoxazol-5-ylpropyl]carbamate.
Among the compounds of general formula (I), one subfamily of compounds is comprised of the compounds corresponding to the general formula (I′):

in which
A is chosen from one or more groups X, Y and/or Z;
X represents a methylene group optionally substituted by one or two C1-6-alkyl, C3-7-cycloalkyl or C3-7-cycloalkyl-C1-3-alkylene groups;
Y represents either a C2-alkenylene group optionally substituted by one or two C1-6-alkyl, C3-7-cycloalkyl or C3-7-cycloalkyl-C1-3-alkylene groups; or a C2-alkynylene group;
Z represents a group of formula:

m represents an integer ranging from 1 to 5;
p and q represent integers and are defined such that p+q is a number ranging from 1 to 5;
n represents an integer ranging from 1 to 7;
R1 represents an R2 group optionally substituted by one or more R3 and/or R4 groups;
R2 represents a group chosen from a pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, naphthyl, quinolinyl, tetrahydroquinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, 2-oxo-3,4-dihydroquinolinyl, 1-oxo-3,4-dihydroisoquinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, cinnolinyl, naphthyridinyl, benzofuranyl, dihydrobenzofuranyl, benzothienyl, dihydrobenzothienyl, indolyl, indolinyl, indazolyl, isoindolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, benzoxadiazolyl, benzothiadiazolyl, pyrrolopyridyl, furopyridyl, thienopyridyl, imidazopyridyl, oxazolopyridyl, thiazolopyridyl, pyrazolopyridyl, isoxazolopyridyl or isothiazolopyridyl;
R3 represents a group chosen from halogen atoms or cyano, nitro, C1-6-alkyl, C1-6-alkoxy, hydroxyl, C1-6-thioalkyl, C1-6-fluoroalkyl, C1-6-fluoroalkoxy, C1-6-fluorothioalkyl, NR5R6, NR5COR6, NR5CO2R6, NR5SO2R6, COR5, CO2R5, CONR5R6, SO2R5, SO2NR5R6 or —O—(C1-3-alkylene)-O— groups;
R4 represents a group chosen from phenyl, phenyloxy, benzyloxy, naphthyl, pyridyl, pyrimidinyl, pyridazinyl or pyrazinyl groups; it being possible for the R4 group or groups to be substituted by one or more R3 groups which are identical to or different from one another;
R5 and R6 represent, independently of one another, a hydrogen atom or a C1-6-alkyl group or form, with the atom or atoms which carry them, a ring chosen from an azetidine, pyrrolidine, piperidine, morpholine, thiomorpholine, azepine or piperazine ring, this ring optionally being substituted by a C1-6-alkyl or benzyl group;
R7 represents a hydrogen atom or a C1-6-alkyl group;
R8 represents a hydrogen atom or a C1-6-alkyl, C3-7-cycloalkyl or C3-7-cycloalkyl-C1-3-alkylene group.
Among the compounds of general formula (I′), a first subgroup of compounds is comprised of the compounds for which:
A is chosen from one or more groups X and/or Y;
X represents a methylene group;
Y represents a C2-alkynylene group;
n represents an integer ranging from 1 to 5;
R1 represents an R2 group optionally substituted by one or more phenyl groups, more particularly by one phenyl;
R2 represents a group chosen from a pyridyl, pyrimidinyl, pyridazinyl, imidazolyl, oxazolyl, oxadiazolyl, naphthyl, quinolinyl, isoquinolinyl, dihydroisoquinolinyl, 2-oxo-3,4-dihydroquinolinyl, indolyl, benzimidazolyl or pyrrolopyridyl;
R7 represents a hydrogen atom or a C1-6-alkyl group;
R8 represents a hydrogen atom or a C1-6-alkyl, C3-7-cycloalkyl or C3-7-cycloalkyl-C1-3-alkylene group.
Among the compounds of general formula (I′), a second subgroup of compounds is comprised of the compounds for which:
A, n and R1 are as defined in the first subgroup defined above;
R7 represents a hydrogen atom;
R8 represents a hydrogen atom or a C1-6-alkyl group, more particularly a methyl.
Mention may be made, among the compounds of general formula (I′), of the following compounds:    2-(methylamino)-2-oxoethyl (5-phenylpyrid-2-yl)methylcarbamate    2-(methylamino)-2-oxoethyl 2-(5-phenylpyrid-2-yl)ethylcarbamate    2-(methylamino)-2-oxoethyl 2-(6-phenylpyrid-3-yl)ethylcarbamate    2-(methylamino)-2-oxoethyl 2-(6-phenylpyridazin-3-yl)ethylcarbamate    2-(methylamino)-2-oxoethyl 2-(2-phenylpyrimidin-5-yl)ethylcarbamate    2-(methylamino)-2-oxoethyl 2-(5-phenylpyrimidin-2-yl)ethylcarbamate    2-(methylamino)-2-oxoethyl 2-(isoquinolin-7-yl)ethylcarbamate    2-(methylamino)-2-oxoethyl 2-(4-phenyl-1H-imidazol-1-yl)ethylcarbamate    2-(methylamino)-2-oxoethyl 2-(2-phenyl-1,3-oxazol-4-yl)ethylcarbamate    2-(methylamino)-2-oxoethyl 2-(5-phenyl-1,2,4-oxadiazol-3-yl)ethylcarbamate    2-amino-2-oxoethyl 3-(pyrid-2-yl)propylcarbamate    2-amino-2-oxoethyl 3-(pyrid-3-yl)propylcarbamate    2-amino-2-oxoethyl 3-(pyrid-4-yl)propylcarbamate    2-amino-2-oxoethyl 3-(pyrimidin-5-yl)propylcarbamate    2-amino-2-oxoethyl 3-(quinolin-2-yl)propylcarbamate    2-amino-2-oxoethyl 3-(quinolin-4-yl)propylcarbamate    2-amino-2-oxoethyl 3-(isoquinolin-1-yl)propylcarbamate    2-amino-2-oxoethyl 3-(isoquinolin-4-yl)propylcarbamate    2-(methylamino)-2-oxoethyl 3-(4-phenyl-1H-imidazol-1-yl)propylcarbamate    2-(methylamino)-2-oxoethyl 3-(1H-benzimidazol-1-yl)propylcarbamate    2-amino-2-oxoethyl 4-(pyrid-2-yl)butylcarbamate    2-amino-2-oxoethyl 4-(pyrid-3-yl)butylcarbamate    2-amino-2-oxoethyl 4-(pyrid-4-yl)butylcarbamate    2-amino-2-oxoethyl 4-(pyrimidin-5-yl)butylcarbamate    2-amino-2-oxoethyl 4-(quinolin-2-yl)butylcarbamate    2-amino-2-oxoethyl 4-(quinolin-4-yl)butylcarbamate    2-amino-2-oxoethyl 4-(isoquinolin-1-yl)butylcarbamate    2-amino-2-oxoethyl 4-(isoquinolin-4-yl)butylcarbamate    2-(methylamino)-2-oxoethyl 4-(1H-benzimidazol-1 -yl)butylcarbamate    2-amino-2-oxoethyl 4-(1H-indol-1-yl)butylcarbamate    2-(methylamino)-2-oxoethyl 4-(1H-indol-1-yl)butylcarbamate    2-amino-2-oxoethyl 4-(1H-pyrrolo[2,3-b]pyrid-1-yl)butylcarbamate    2-(methylamino)-2-oxoethyl 4-(1H-pyrrolo[2,3-b]pyrid-1-yl)butylcarbamate    2-(methylamino)-2-oxoethyl 4-(3,4-dihydroisoquinolin-2(1H)-yl)butylcarbamate    2-amino-2-oxoethyl 4-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)butylcarbamate    2-(methylamino)-2-oxoethyl 4-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)butylcarbamate    2-amino-2-oxoethyl 5-(pyrid-2-yl)pentylcarbamate    2-amino-2-oxoethyl 5-(pyrid-4-yl)pentylcarbamate    2-amino-2-oxoethyl 5-(pyrimidin-5-yl)pentylcarbamate    2-amino-2-oxoethyl 5-(quinolin-2-yl)pentylcarbamate    2-amino-2-oxoethyl 5-(quinolin-4-yl)pentylcarbamate    2-amino-2-oxoethyl 5-(isoquinolin-1-yl)pentylcarbamate    2-amino-2-oxoethyl 5-(isoquinolin-4-yl)pentylcarbamate    2-amino-2-oxoethyl [3-(naphth-1 -yl)prop-2-yn-1-yl]carbamate    2-(methylamino)-2-oxoethyl [3-(naphth-1-yl)prop-2-yn-1-yl]carbamate    2-amino-2-oxoethyl [5-(naphth-1-yl)pent-4-yn-1-yl]carbamate    2-(methylamino)-2-oxoethyl [5-(naphth-1 -yl)pent-4-yn-1-yl]carbamate.
The compounds of general formula (I) can comprise one or more asymmetric carbons. They can exist in the form of enantiomers or of diastereoisomers. These enantiomers and diastereoisomers, and their mixtures, including the racemic mixtures, form part of the invention.
The compounds of formula (I) can exist in the form of bases or of addition salts with acids.
Such addition salts form part of the invention.
These salts are advantageously prepared with pharmaceutically acceptable acids but the salts of other acids, of use, for example, for the purification or the isolation of the compounds of formula (I), also form part of the invention.
The compounds of general formula (I) can exist in the form of hydrates or of solvates, namely in the form of combinations or of associations with one or more molecules of water or with a solvent. Such hydrates and solvates also form part of the invention.
In the context of the invention:                Ct-z, where t and z can take the values from 1 to 7, is understood to mean a carbon chain which can have from t to z carbon atoms, for example C1-3 a carbon chain which can have from 1 to 3 carbon atoms;        alkyl is understood to mean a saturated, linear or branched, aliphatic group; for example a C1-6-alkyl group represents a linear or branched carbon chain of 1 to 6 carbon atoms, more particularly a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl or hexyl;        alkylene is understood to mean a saturated, linear or branched, divalent alkyl group, for example a C1-3-alkylene group represents a linear or branched divalent carbon chain of 1 to 3 carbon atoms, more particularly a methylene, ethylene, 1-methylethylene or propylene;        cycloalkyl is understood to mean a cyclic alkyl group, for example a C3-7-cycloalkyl group represents a cyclic carbon group of 3 to 7 carbon atoms, more particularly a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl;        alkenylene is understood to mean an unsaturated divalent aliphatic group comprising 2 carbons, more particularly an ethenylene;        C2-alkynylene is understood to mean a —C≡C— group;        alkoxy is understood to mean an —O-alkyl group comprising a saturated, linear or branched, aliphatic chain;        thioalkyl is understood to mean an —S-alkyl group comprising a saturated, linear or branched, aliphatic chain;        fluoroalkyl is understood to mean an alkyl group, one or more hydrogen atoms of which have been substituted by a fluorine atom;        fluoroalkoxy is understood to mean an alkoxy group, one or more hydrogen atoms of which have been substituted by a fluorine atom;        fluorothioalkyl is understood to mean a thioalkyl group, one or more hydrogen atoms of which have been substituted by a fluorine atom;        halogen is understood to mean a fluorine, a chlorine, a bromine or an iodine.        
The compounds of the invention can be prepared according to various methods illustrated by the schemes which follow.

A first method (Scheme 1) for producing the compounds of general formula (I) consists in reacting an amine of general formula (II), in which R1, A and n are as defined in the general formula (I), with a carbonate of general formula (II) in which V represents a hydrogen atom or a nitro group, R7 is as defined in the general formula (I) and R represents a methyl or ethyl group. The carbamate-ester of general formula (IV) thus obtained is subsequently converted to the compound of general formula (I) by aminolysis using an amine of general formula R8NH2, where R8 is as defined in the general formula (I). The aminolysis reaction can be carried out in a solvent, such as methanol or ethanol, or a mixture of solvents, such as methanol and tetrahydrofuran.
Another method (Scheme 2) for producing the compounds of general formula (I) consists in reacting a derivative of general formula (V), in which R1, n and A are as defined in the general formula (I) and W represents a hydroxyl, mesylate or tosylate group or a chlorine, bromine or iodine atom, with an oxazolidinedione of general structure (VI), in which R7 is as defined in the general formula (I), to provide the oxazolidinedione derivative of general structure (VII).
In the case where W represents a hydroxyl group, the reaction can be carried out according to the conditions of Mitsunobu (Synthesis, 1981, 1-28), for example, by the action of diethyl or diisopropyl azodicarboxylate in the presence of triphenylphosphine. In the case where W represents a chlorine, bromine or iodine atom or a mesylate or tosylate group, the reaction can be carried out in the presence of a base, such as 1,1,3,3-tetramethylguanidine, sodium hydride or sodium tert-butoxide, in a solvent, such as tetrahydrofuran, acetonitrile or dimethylformamide, at a temperature of between 0° C. and 80° C. The oxazolidinedione derivative of general formula (VII) thus obtained is subsequently converted to the compound of general formula (I) by aminolysis using an amine of general formula R8NH2, where R8 is as defined in the general formula (I).

The compounds of general formula (I), (IV) and (VII) in which R1 represents a group of aryl-aryl, aryl-heteroaryl, heteroaryl-aryl or heteroaryl-heteroaryl type can also be prepared by reaction of the corresponding compounds of general formula (I), (IV) or (VII) for which R2 is substituted by a chlorine, bromine or iodine atom or by a triflate group in the position where the R4 group has to be introduced with an aryl- or heteroarylboronic acid derivative according to the Suzuki reaction conditions (Chem. Rev., 1995, 95, 2457-2483) or with an aryl- or heteroaryltrialkylstannane derivative according to the Stille reaction conditions (Angew. Chem. Int. Ed., 1986, 25, 504-524).
The carbonates of general formula (III) can be prepared according to any method described in the literature, for example by reaction of an alcohol of general formula HOCHR7COOR, where R represents a methyl or ethyl group, with phenyl or 4-nitrophenyl chloroformate in the presence of a base, such as triethylamine or diisopropylethylamine.
The compounds of general formulae (II), (V) and (VI) and the amines of general formula R8NH2, when their method of preparation is not described, are commercially available or are described in the literature or can be prepared according to various methods described in the literature or known to a person skilled in the art.
The compounds of general formula (IV) in which n, A, R1 and R7 are as defined in the general formula (I) and R represents a methyl or ethyl group are novel and also form part of the invention, the following compounds being excluded:    ethyl 2-[({[2-(5-hydroxy-1H-indol-3-yl)ethyl]amino}carbonyl)oxy]propanoate;    ethyl 2-[({[2-[5-(phenylmethoxy)-1H-indol-3-yl]ethyl]amino}carbonyl)oxy]propanoate.
The compounds of general formula (IV) are of use as synthetic intermediates for the preparation of the compounds of general formula (I).
The compounds of general formula (VII) in which n, A, R1 and R7 are as defined in the general formula (I) are novel and also form part of the invention, the following compounds being excluded:    2-[2-(2,4-dioxo-3-oxazolidinyl)ethyl]-1-methylpyridinium iodide;    2-[2-(2,4-dioxo-3-oxazolidinyl)ethyl]-5-ethyl-1-methylpyridinium iodide;    4-[2-(2,4-dioxo-3-oxazolidinyl)ethyl]-1-methylpyridinium iodide;    5-methyl-3-[2-(4-pyridyl)ethyl]-2,4-oxazolidinedione hydrochloride;    5-methyl-3-[2-(2-pyridyl)ethyl]-2,4-oxazolidinedione hydrochloride;    3-[5-(imidazo[1,2-a]pyridin-5-yl)pentyl]-2,4-oxazolidinedione;    3- [2-(5-methyl-4-thiazolyl)ethyl]-2,4-oxazolidinedione;    3-[2-(1H-pyrrol-2-yl)ethyl]-2,4-oxazolidinedione;    3-[2-(2-thienyl)ethyl]-2,4-oxazolidinedione;    3-[3-(2-thienyl)propyl]-2,4-oxazolidinedione;    3-[4-(2-thienyl)butyl]-2,4-oxazolidinedione;    5-methyl-3-[2-(2-thienyl)ethyl]-2,4-oxazolidinedione;    5-ethyl-3-[2-(2-thienyl)ethyl]-2,4-oxazolidinedione;    3-[2-(3-thienyl)ethyl]-2,4-oxazolidinedione;    3-[2-(5-methyl-2-thienyl)ethyl]-2,4-oxazolidinedione;    3-[2-(5-acetyl-2-thienyl)ethyl]-2,4-oxazolidinedione;    3-[2-(5-bromo-2-thienyl)ethyl]-2,4-oxazolidinedione;    5-[2-(2,4-dioxo-3-oxazolidinyl)ethyl]-2-thiophenecarbaldehyde;    3-[3-(1-indolinyl)propyl]-2,4-oxazolidinedione;    3-[3-(1-indolinyl)propyl]-5-methyl-2,4-oxazolidinedione;    3-[2-(2-pyridyl)ethyl]-2,4-oxazolidinedione;    3-[2-(5-ethyl-2-pyridyl)ethyl]-5-methyl-2,4-oxazolidinedione;    5-ethyl-3-[2-(5-ethyl-2-pyridyl)ethyl]-2,4-oxazolidinedione;    3-[2-(5-ethyl-2-pyridyl)ethyl]-5-isopropyl-2,4-oxazolidinedione;    3-[2-(4-pyridyl)ethyl]-2,4-oxazolidinedione;    5-ethyl-3-[2-(4-pyridyl)ethyl]-2,4-oxazolidinedione;    5-ethyl-3-[2-(2-pyridyl)ethyl]-2,4-oxazolidinedione;    5-isopropyl-3-[2-(4-pyridyl)ethyl]-2,4-oxazolidinedione;    5-isopropyl-3-[2-(2-pyridyl)ethyl]-2,4-oxazolidinedione;    3-[2-(5-ethyl-2-pyridyl)ethyl]-2,4-oxazolidinedione.
The compounds of general formula (VII) are of use as synthetic intermediates for the preparation of the compounds of general formula (I).
A subgroup of compounds of general formula (VII) is composed of the compounds for which:
n, A, R1 and R7 are as defined in the general formula (I) provided that:                when R2 is a pyrrolyl, imidazo[1,2-a]pyridyl or indolinyl group, then R2 is substituted by one or more R3 and/or R4 groups;        when R2 is a pyridyl group, then R2 is substituted by one or more R3 and/or R4 groups where R3 is other than a methyl or than an ethyl;        when R2 is a thienyl group, then R2 is substituted by one or more R3 and/or R4 groups where R3 is other than a bromine, than a methyl or than a CHO or COCH3 group;        when R2 is a thioazolyl group substituted by an R3 group, then R3 is other than a methyl.        
The examples which will follow illustrate the preparation of a few compounds of the invention. These examples are not limiting and only illustrate the invention. The microanalyses, the IR and NMR spectra and/or the LC-MS (Liquid Chromatography coupled to Mass Spectroscopy) confirm the structures and the purities of the compounds obtained.
M.p. (° C.) represents the melting point in degrees Celsius.
The numbers shown in brackets in the titles of the examples correspond to those in the 1st column in the table below.